1. Technical Field
This disclosure relates to surface-coated implantable medical devices.
2. Description of the Related Art
Implantable medical devices such as implantable biosensors, breast implants, prostheses, surgical mesh implants, catheters, and neuromodulation leads, once implanted into a body, frequently induce an inflammatory reaction of the body. This common problem is called the foreign body response (FBR). In the first hours of the FBR, host macrophages are attracted to the surface of the implant. The macrophages arrive in sufficient numbers to spread over all surfaces of the implant that interface with the host tissue. When the surface of the device is smooth and impermeable to cells, these macrophages trigger a cascade of cytokines and chemokines that recruit fibroblasts and other extracellular matrix-building cells to the tissue adjacent to the implant. Typically, the end result of the FBR is the formation of a dense, fibrous, largely avascular capsule that partially or completely surrounds the device. This foreign body encapsulation can effectively isolate the implantable device from the surrounding tissue, physically, chemically, and electrically.
FBR limits the performance and operating lives of most implantable devices, which limitation is particularly debilitating in devices that are designed to continuously monitor or report data of measurements to an external data processing unit. For example, there have been many attempts to develop implantable devices that can continuously record blood glucose monitoring data; however, the FBR effects have frustrated these efforts. Similarly, proper functioning of neuromodulation electrodes and other electrostimulation devices is adversely affected by the FBR. Buildup of dense fibrous capsule tissue increases the electrical impedance from the electrodes to surrounding tissue and shortens the battery life.
Tissue implants used in cosmetic and reconstructive surgeries are another type of implantable devices, the functions of which can be adversely affected by the FBR. In particular, fibrous capsule can form and contract around the implant (e.g., breast implant), causing it to harden. The condition often requires the implant to be surgically removed. Barone F. E. et al., Plast. Reconstr. Surg. 90:77 (1992). Surgical trauma further increases the risk of capsular contracture, and the problem is most likely to occur in cases of reconstructive surgery. Henriksen T. F. et al., Ann. Plast. Surg. 54:343 (2005). Using open textured surfaces with roughness on the order of a pattern of 300 μm periodicity has significantly reduced the incidence of capsular contracture; however, the problem remains in 10 to 20% of all breast implant surgeries. Barnsley G P et al., Plast. Reconstr. Surg. 117:2182 (2006).
It has been shown that the biological response (e.g., FBR) to implanted biomaterials depends on the architecture of the biomaterial. Paul N. E. et al., Biomaterials 29:4056-64 (2008). In particular, porous biomaterials with pore sizes on the order of cellular dimensions have been shown to alter the FBR. For example, porous biomaterials with a pore size that is large enough to allow macrophage penetration was shown to increase vascularity in the capsule tissue. Brauker J. H. et al., J. Biomed. Mater. Res. 29:1517 (1995). Increased vascularity was shown to correlate with improved diffusion and plasma-exchange properties. Sharkawy A. A. et al., J. Biomed. Mater. Res.:586 (1998). It was also recognized that a minimum pore size that allows colonization by host macrophages within the pore structure maximizes the density of new vessels within the scaffold, and elicits an FBR with significantly reduced capsule thickness than is seen when larger pore sizes, or pore sizes too small to permit cellular ingrowth, are used. Marshall A. J. et al., Polymer Preprints 45:100 (2004); Madden L. R. et al., Proc. Nat. Acad. Sci. 107(34):15211 (2010). These pore geometries have been shown to attract high concentrations of infiltrating macrophages. Marshall A. J. et al., supra; Tsai A., Engineering biomaterial interfaces to control foreign body response: reducing giant cell formation and understanding host response to porous materials, Ph.D. Dissertation, University of Washington (2007). It has been shown that the macrophages that colonize microporous structures or micro-textured surfaces assume an alternative phenotype that includes an altered cytokine release profile. For example, it has been shown that macrophages cultured on a micro-textured surface comprising an array of 10-μm diameter pillars separated by 20-μm spacing become activated and release both pro-inflammatory and anti-inflammatory cytokines Paul N. E. et al., supra. Further, evidence that porous materials promote angiogenic and anti-fibrotic activities has been found by measuring cytokine release profiles from tissues surrounding implants. Tsai A., supra.
Even when porous biomaterials are used in conjunction with medical devices, some degree of encapsulation still occurs. Rosengren, A. et al., J. Biomed. Matl. Res. 67a:918-926 (2003). Thus, the FBR remains a formidable problem for many types of implantable devices such as biosensors and tissue implants.